Published: December 2010 - The final oral presentation at the 12th International Workshop on Adverse Drug Reactions and
Co-Morbidities in HIV included important information for clinical management for facial lipoatrophy, reporting a 10% complication from Bio-Alcamid
gel implants. This should result in the product no longer being used in the UK.

Jeya Nadarajah from University of Toronto presented results from a retrospective review to determine the incidence of
complications in 263 HIV-positive people (during 375 person years of follow up) who were treated with Bio-Alcamid in Toronto. [1]

Bio-Alcamid polyalkylimide gel is marketed as a biochemically inert, non-reabsorbing polymer that can be injected
subcutaneously under aseptic conditions in up to 25 mL volume. The use of larger volumes made this an option for patients with more severe
lipoatrophy, when lower volume resorbable fillers like poly-L-lactic acid (New-Fill) require many more treatments. After injection, the
material encapsulates within a 0.2 mm collagen membrane as an 'endoprosthesis'. Although promoted as semi-permanent and extractable,
this becomes an increasingly difficult procedure the longer the implant has been in place.

Bio-Alcamid polyalkylimide gel is marketed as a biochemically inert, non-reabsorbing polymer that can be injected subcutaneously under aseptic conditions
in up to 25 mL volume. The use of larger volumes made this an option for patients with more severe lipoatrophy, when lower volume resorbable fillers like
poly-L-lactic acid (New-Fill) require many more treatments. After injection, the material encapsulates within a 0.2 mm collagen membrane as an
'endoprosthesis'. Although promoted as semi-permanent and extractable, this becomes an increasingly difficult procedure the longer the implant
has been in place.

Previous complications have been reported in case studies [2, 3, 4, 5] and a retrospective analysis published in 2009 (including
270 HIV-positive patients) reported a 4.8% complication rate that given "the severity of the complications, and the difficulty in treating them too high a
risk for a cosmetic treatment" [6].

Of the 263 people in the Toronto group, most had their first treatment in 2005 (~ n=100) or 2006 (~n=85). Demographic and treatment data available for
240 people included median age was 49 (IQR 44-54), 96% were male, 95% of treatments were to the cheeks and temples, with a median of four injections
injections using a median of 11 mL (10-15 mL).

Antibiotic prophylaxis using Cephalexin for five days was provided for all treatments including the 145 patients (60%) who required subsequent touch-up
treatment.

At least one infectious complication was reported for 51/263 patients (19%) with 13 definite (5%) and 38 probable. This was calculated as an incidence
rate of 0.14 infections per person year of follow-up and a definite incidence rate of 0.034 per PYFU. Time to complication from last injection indicated
that most were late complications (after 1-4 years). Secondary touch-up treatment was most significant risk factor for complications: 86% of people
with complications had had subsequent touch-up treatment compared to 54% of people without complications (p<0.0001).

Medical management with antibiotics for an average 4 weeks (range 7 days to 19 months), with two patients remaining on chronic therapy.
Surgical procedures including incision and drainage, aspiration or debridement were performed in 22 people and included 7 full and 15 partial
removals of Bio-Alcamid. Approximately two-thirds of the infections (n=35; 68%) resolved and one-third relapsed (n=16, 31%).

The study limitations included that this was retrospective observational data and that the researchers only identified centers with large
volumes - both potentially underestimating incidence. Also, data were extracted from surgical charts that often missed important variables and this
limited clinical diagnosis in absence of microbiologic confirmation.

comment

This study highlights the difficulty in recording the safety of treatments that are provided in private clinics, often for products for which there
are little safety and efficacy data from clinical trials.

The private clinic in the UK that has treated several hundred men in the UK has since discontinued its use [7], as have clinics in Spain, Canada
and Mexico. UK complications from private practice have usually been picked up and managed by NHS clinics with expertise on treating HIV-related
lipoatrophy.

Because Bio-Alcamid removal becomes more difficult and traumatic the longer the implants have been in place, patients who received treatment need
to be advised of the importance of minimising the risk of future complications. This includes avoiding non-sterile needle puncture from dental treatment
or supplementary treatment for facial lipoatrophy, and reducing risk of facial trauma.

In the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) are assessing the safety of Bio-Alcamid. UK cases should be notified
by heathcare professional or patients using the MHRA Yellow Card scheme ( yellowcard.mhra.gov.uk ).

An estimated 30 products (classed as medical devices rather than medicines) are being used in Europe but, unlike New-fill, few have been studied in controlled trials for HIV-related lipoatrophy.

Higher volume treatment using PMMA (polymethylacrylate) has been reported (including at the Lipodystrophy workshop [8]) in HIV-related lipoatrophy (including both facial and buttock restoration). [9]